The objective of this research project is to elucidate the photochemical and photobiological mechanisms whereby light (UVA and visible radiation) alone or in the presence of endogenous or exogenous photosensitizers exerts either toxic or therapeutic effects. UVA-induced apoptosis in keratinocytes is associated with a decrease in intracellular GSH and a concomitant increase in extracellular GSH produced by GSH efflux. We have used microarray technology to determine changes in gene expression in HaCaT human keratinocytes after UVA treatment. We have found in human HaCaT keratinocytes that exposure to UVA induces the EGF receptor internalization and down-regulation without receptor phosphorylation and ubiquitination. Berberine, the active constituent of the herbal medicine Goldenseal, commonly used in lotions and eyewashes, kills keratinocytes and damages DNA upon UV radiation. Juglone (5-hydroxy-1,4-naphthoquinone), found in herbal skin and hair products derived from Black Walnut, is metabolized by keratinocytes to a semiquinone free radical which reacts with oxygen to generate superoxide and the hydroxyl radical. 7-Dehydrocholesterol sensitizes keratinocytes to UVA and is probably responsible for the photosensitivity of Smith-Lemli-Opitz syndrome (SLOS) patients. A2E, a lipid degradation product found in lipofuscin granules deposited in the retina, is photoprotective in the young eye but may be phototoxic in older eyes.